Abstract
Background: A safe and effective vaccine against human leishmaniasis still requires the identification of better antigens for immunization and adequate models to evaluate the immune response. To support vaccine development, this work tested the immunogenicity of 10 different peptides derived from the proteome of Leishmania braziliensis, which were selected by their in silico affinity to MHC complexes.Research design and Methods: Comparative cell proliferation assays were performed by culturing, in the presence of each peptide, PBMC cells from subclinical subjects (SC), cutaneous leishmaniasis patients with active disease (AD), post-treatment (PT) individuals, and healthy controls. Culture supernatants were then used for Th1, Th2, and Th17 cytokine measurements. Cells from selected PT samples were also used to assess the expression, by T cells, of the T-bet Th1 transcription factor.Results: A robust cell proliferation was observed for the SC group, for all the tested peptides. The levels of Th1 cytokines were peptide-dependent and had substantial variations between groups, where, for instance, IFN-γ and TNF levels were some of the highest, particularly on PT cultures, when compared to IL-2. On the other hand, Th2 cytokines displayed much less variation. IL-6 was the most abundant among all the evaluated cytokines while IL-4 and IL-10 could be found at much lower concentrations. IL-17 was also detected with variations in SC and AD groups. T-bet was up-regulated in CD4+ and CD8+ T cells from the PT group after stimulation with all peptides.Conclusions: The peptide epitopes can differentially stimulate cells from SC, AD, and PT individuals, leading to distinct immune responses.
Highlights
The leishmaniasis are an important group of neglected tropical diseases (NTDs) [1, 2] caused by protozoans of the genus Leishmania
VL is mainly caused by L. donovani and L. infantum, while many different Leishmania species are involved in the development of CL, such as L. braziliensis and L. major (Old World)
Samples were clustered into four different groups: subclinical (SC, n = 10), corresponding to those who lived in endemic regions, positive for the Leishman Skin Test (LST), and who had no history of clinical disease; active disease (AD, n = 8), who were diagnosed patients with CL; post-treatment (PT, n = 13), patients treated for up to 1 year and who were considered clinically cured; and one group of healthy individuals living in non-endemic regions for leishmaniasis, considered as negative controls (n = 5)
Summary
The leishmaniasis are an important group of neglected tropical diseases (NTDs) [1, 2] caused by protozoans of the genus Leishmania. These diseases are endemic in 98 countries and territories, with an annual incidence of 1.5–2 million cases and with at least 350 million people living in areas with a higher transmission risk. CL is more widespread and responsible for afflicting a more substantial number of individuals. This disease is usually relatively benign, it may cause disfigurement and loss of productivity [4]. Cells from selected PT samples were used to assess the expression, by T cells, of the T-bet Th1 transcription factor
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